Roche’s Kidney Disease Drug Succeeds in Phase 3 Trial, Setting Up Market Competition With Novartis

Swiss drugmaker Roche has met the primary endpoint in a Phase 3 trial of zepasarsen, a candidate treatment for kidney disease. The result is expected to set up competition with Novartis in a potential blockbuster market.

According to U.S. pharmaceutical trade publication Fierce Biotech on the 23rd (local time), Roche said zepasarsen, which it is developing with Ionis Pharmaceuticals, met the primary endpoint in a Phase 3 trial in patients with primary immunoglobulin A nephropathy (IgAN).

In a prespecified interim analysis, patients who received monthly injections of zepasarsen had a significant reduction in proteinuria, measured by the 24-hour urine protein-to-creatinine ratio (UPCR), compared with the placebo group. Safety and tolerability data were consistent with those from previous trials.

The Phase 3 IMAGINATION study will remain blinded to assess changes in kidney function at week 105. Based on previous research linking reduced proteinuria with preservation of long-term kidney function, Roche plans to discuss next steps with regulators.

Jay Garg, Roche’s global head of renal, rheumatology and cardiovascular, said at an immunology event in March that he hoped the week 37 proteinuria data would "lead to accelerated approval."

Estimates of zepasarsen’s commercial potential vary. Bruno Eschli, Roche’s head of investor relations, said at the March event that "most analyst models project sales of 400 million euros by 2030." Roche offered a more optimistic forecast, putting peak sales at 1 billion to 2 billion euros.

Zepasarsen is an antisense oligonucleotide that inhibits production of complement factor B, which is elevated in patients with IgAN. Inhibiting factor B can prevent the complement system from damaging kidney cells.

Novartis’ Fabhalta also inhibits factor B. The U.S. Food and Drug Administration (FDA) granted Fabhalta accelerated approval for IgAN in 2024 and converted it to full approval this year. Fabhalta is taken orally twice daily, while zepasarsen is administered by subcutaneous injection once a month. Fabhalta can raise cholesterol, but zepasarsen did not affect cholesterol in a Phase 2 trial.

Roche secured a license to zepasarsen for IgAN in 2022, paying Ionis an upfront fee of $55 million. The deal followed Roche’s 2018 payment of $75 million for an option on the asset. GlaxoSmithKline (GSK) previously held the rights to the program but relinquished them in 2017.